The proposed research is intended to answer the questions: (1) What is the nature of the defectiveness of adenovirus replication in monkey cells? (2) What are the mechanisms by which one virus enhances the growth and oncogenicity of another? (3) What portion of the adenovirus and SV40 genomes are responsible for the oncogenicity of these viruses? These questions are to be answered by: (1) Biophysical and immunochemical analysis of the nucleic acid and protein products of defective adenovirus replication in monkey cells, in the presence and absence of SV40 co-infection. (2) Study of the segment of SV40 genome, or product of SV40 replication responsible for overcoming the block to efficient adenovirus replication. Both SV40 virus and the partial SV40 genome in the adenovirus-SV40 hybrid virus E46 plus will be used. (3) Analysis of the adenovirus and SV40 genomes using ultracentrifugation, RNA-DNA hybridization and temperature sensitive (ts) mutants will be carried out. It is hoped that these studies will succeed in isolating and characterizing the oncogenic genome of adenovirus and SV40.